Comparative Wound Healing Processes in Plants and Animals: Bioinspired Strategies for Advancing Regenerative Medicine
Fatemeh Najafi, Natália Aparecida de Paula, Filipe Rocha Lima, Marcio Fronza, Carem Gledes Vargas Rechia, Marco Andrey Cipriani FradeWound healing is a fundamental biological process essential to maintaining structural integrity and survival across both plant and animal life. Despite the profound evolutionary distance separating these kingdoms, wound healing provides one of those momentous occasions when these biological universes collide, revealing significant evolutionary parallels in the core mechanisms of healing, despite clear molecular and physiological differences. However, two challenges have hindered systematic cross-kingdom comparisons. First, unlike animal wound healing, the major phases of plant wound healing have not been organized into a universally accepted classification. Second, no comparative framework exists for systematically comparing wound-healing processes across plant and animal kingdoms. To address these challenges, we developed a comparative classification framework that organizes wound healing into three functional phases: (1) bioelectrical signaling, (2) immune responses, and (3) tissue formation and remodeling. This classification defines the major phases of plant wound healing, while the comparative framework establishes a common basis for systematic cross-kingdom comparison. Through comparative analysis, multiple shared cellular and molecular mechanisms were identified. These findings led to a conceptual model termed the hybrid-wound healing system, integrating plant- and animal-derived regenerative responses and providing a theoretical basis for future bioinspired regenerative strategies. Within this system, living plant stem cells are proposed as central biological components that may potentially act as intelligent pharmaceutical microfactories, releasing bioactive molecules in suitable microenvironments. This approach represents a hypothetical future strategy requiring extensive preclinical validation to strategies based on extracts, conditioned media, extracellular vesicles, or isolated bioactive compounds. Collectively, this descriptive review establishes a conceptual foundation for future investigations in plant biology, wound healing, and regenerative medicine.